Evidence map›Paper›PMID 26751286›Full record

ArticleNature cell biology2016

De novo DNA methylation drives 5hmC accumulation in mouse zygotes.

Rachel Amouroux, Buhe Nashun, Kenjiro Shirane, Shoma Nakagawa, Peter Ws Hill, Zelpha D'Souza, Manabu Nakayama, Masashi Matsuda, Aleksandra Turp, Elodie Ndjetehe and 5 more

Open access · greenAbstract readLetter
In one paragraph

Article in Nature cell biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 134 papers.

0numbers the graph read from it
0cells of the map it votes in
134citing papers in PubMed
19.5field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

134 citing papers in PubMed, 235 citations in OpenAlex.

  1. Article
  2. Article
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  4. The multi-omics regulatory landscape of human early embryogenesis.Cellular and molecular life sciences : CMLS · 2026
    Review
  5. Maternal O-GlcNAc Transferase Is Required for the Asymmetry of Epigenetic Modifications in Mouse Zygotes.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Article
  6. Exit from totipotency in mammals: an epigenetic perspective.Frontiers in cell and developmental biology · 2026
    Review
  7. Article
  8. Article
  9. Review
  10. Review
  11. Article
  12. Review
  13. Article
  14. Perturbing nuclear glycosylation in the mouse preimplantation embryo slows down embryonic development.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  15. Article
  16. Review
  17. Article
  18. Review
  19. Article
  20. Article

74 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 4 institutions in 2 countries.

Rachel AmourouxMedical Research Council Clinical Sciences Centre, Imperial College London, London W12 0NN, United Kingdom.
Buhe Nashun *Medical Research Council Clinical Sciences Centre, Imperial College London, London W12 0NN, United Kingdom.
Kenjiro Shirane *Division of Epigenomics and Development, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Shoma Nakagawa *Institute of Reproductive and Developmental Biology, Imperial College London, London W12 0NN, United Kingdom.
Peter Ws HillMedical Research Council Clinical Sciences Centre, Imperial College London, London W12 0NN, United Kingdom.
Zelpha D'SouzaMedical Research Council Clinical Sciences Centre, Imperial College London, London W12 0NN, United Kingdom.
Manabu NakayamaChromosome Engineering Team, Department of Technology Development, Kazusa DNA Research Institute, 2-6-7 Kazusa-Kamatari, Kisarazu, Japan.
Masashi MatsudaLaboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences, 1-7-22 Suehiro, Tsurumi-ku, Yokohama, Japan.
Aleksandra TurpMedical Research Council Clinical Sciences Centre, Imperial College London, London W12 0NN, United Kingdom.
Elodie NdjeteheMedical Research Council Clinical Sciences Centre, Imperial College London, London W12 0NN, United Kingdom.
Vesela EnchevaMedical Research Council Clinical Sciences Centre, Imperial College London, London W12 0NN, United Kingdom.
Nobuaki R KudoInstitute of Reproductive and Developmental Biology, Imperial College London, London W12 0NN, United Kingdom.
Haruhiko KosekiLaboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences, 1-7-22 Suehiro, Tsurumi-ku, Yokohama, Japan.
Hiroyuki SasakiDivision of Epigenomics and Development, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Petra HajkovaMedical Research Council Clinical Sciences Centre, Imperial College London, London W12 0NN, United Kingdom.
Imperial College London · GBKyushu University · JPRIKEN Center for Integrative Medical Sciences · JPKazusa DNA Research Institute · JP

Funding

Medical Research Council G0901046Medical Research Council MC_U120092689
6 · The paper itself

Abstract

Zygotic epigenetic reprogramming entails genome-wide DNA demethylation that is accompanied by Tet methylcytosine dioxygenase 3 (Tet3)-driven oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC; refs 1-4). Here we demonstrate using detailed immunofluorescence analysis and ultrasensitive LC-MS-based quantitative measurements that the initial loss of paternal 5mC does not require 5hmC formation. Small-molecule inhibition of Tet3 activity, as well as genetic ablation, impedes 5hmC accumulation in zygotes without affecting the early loss of paternal 5mC. Instead, 5hmC accumulation is dependent on the activity of zygotic Dnmt3a and Dnmt1, documenting a role for Tet3-driven hydroxylation in targeting de novo methylation activities present in the early embryo. Our data thus provide further insights into the dynamics of zygotic reprogramming, revealing an intricate interplay between DNA demethylation, de novo methylation and Tet3-driven hydroxylation.

Indexed as

Cellular ReprogrammingDNA MethylationEpigenesis, Genetic5-MethylcytosineAnimalsBiomarkersChromatography, LiquidCytosineDioxygenasesDNA-Binding ProteinsDNA (Cytosine-5-)-Methyltransferase 1DNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3AEmbryo Culture TechniquesFertilization in VitroFluorescent Antibody Technique5-hydroxymethylcytosine5-MethylcytosineBiomarkersCytosineDioxygenasesDNA-Binding ProteinsDNA (Cytosine-5-)-Methyltransferase 1DNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3ADnmt1 protein, mouseDnmt3a protein, mouseProto-Oncogene ProteinsTet3 protein, mouse

Identifiers

PMID26751286
PMCPMC4765106
OpenAlexW2233226906

What OpenQuestion holds

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Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.